9-71685395-TAAAAAAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr9-71685395-TAAA-T
• rs36080695
• NM_013390.3:c.3956-5_3956-3delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_013390.3(CEMIP2):​c.3956-5_3956-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,177,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: CEMIP2 NM_013390.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 3 publications found

Genes affected

CEMIP2 (HGNC:11869): (cell migration inducing hyaluronidase 2) This gene encodes a type II transmembrane protein that belongs to the interferon-induced transmembrane (IFITM) protein superfamily. The encoded protein functions as a cell surface hyaluronidase that cleaves extracellular high molecular weight hyaluronan into intermediate size fragments before internalization and degradation in the lysosome. It also has an interferon-mediated antiviral function in humans through activation of the JAK STAT signaling pathway. The activation of this gene by transcription factor SOX4 in breast cancer cells has been shown to mediate the pathological effects of SOX4 on cancer progression. Naturally occurring mutations in this gene are associated with autosomal recessive non-syndromic hearing loss. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP2	NM_013390.3	c.3956-5_3956-3delTTT		splice_region_variant, intron_variant	Intron 23 of 23	ENST00000377044.9	NP_037522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMIP2	ENST00000377044.9	c.3956-5_3956-3delTTT		splice_region_variant, intron_variant	Intron 23 of 23	1	NM_013390.3	ENSP00000366243.4

Frequencies

GnomAD3 genomes AF: 0.00000859 AC: 1 AN: 116354 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000169

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000315 AC: 334 AN: 1061472 Hom.: 0 AF XY: 0.000365 AC XY: 185 AN XY: 507342

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000135 AC: 3 AN: 22232

American (AMR) AF: 0.00139 AC: 16 AN: 11524

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 13 AN: 15016

East Asian (EAS) AF: 0.000153 AC: 4 AN: 26186

South Asian (SAS) AF: 0.00161 AC: 50 AN: 31152

European-Finnish (FIN) AF: 0.000622 AC: 15 AN: 24130

Middle Eastern (MID) AF: 0.000339 AC: 1 AN: 2952

European-Non Finnish (NFE) AF: 0.000247 AC: 219 AN: 885102

Other (OTH) AF: 0.000301 AC: 13 AN: 43178

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000859 AC: 1 AN: 116354 Hom.: 0 Cov.: 0 AF XY: 0.0000185 AC XY: 1 AN XY: 54084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29244

American (AMR) AF: 0.00 AC: 0 AN: 10662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3084

East Asian (EAS) AF: 0.00 AC: 0 AN: 4212

South Asian (SAS) AF: 0.00 AC: 0 AN: 3512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.0000169 AC: 1 AN: 59300

Other (OTH) AF: 0.00 AC: 0 AN: 1534

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36080695; hg19: chr9-74300311;